¹Lahey Clinic, Burlington, MA, USA, ²Dendreon Corporation, Seattle, WA, USA

Background: Sipuleucel-T is an autologous active cellular immunotherapy being developed by Dendreon Corporation and is designed to elicit a specific T cell immune response against prostatic acid phosphatase in men with advanced prostate cancer. Two identically designed randomized, double-blind, placebo-controlled Phase 3 trials, D9901 (n=127) and D9902A (n=98), have been conducted in men with metastatic, androgen independent prostate cancer (AIPC).
Methods: Subjects were randomized (2:1) to sipuleucel-T or placebo. Each subject underwent 3 standard leukaphereses (Weeks 0, 2, and 4) and each product was administered in physician offices approximately 2 days later. Eligible subjects had tumor progression following hormonal therapy and no visceral metastases. The primary endpoint was time to objective disease progression (TTP) and all subjects were followed for overall survival for 3 years after randomization.
Results: Though there was not a statistically significant difference in TTP between sipuleucel-T and placebo in either study, in D9901, sipuleucel-T resulted in a statistically significant overall survival advantage compared with placebo (P=0.010, log rank; HR=1.7). A Cox proportional hazards regression (PHR) model that incorporated prognostic variables considered predictive of survival also resulted in a survival advantage for sipuleucel-T (P=0.002, Wald’s; HR=2.1). After 36 months, 34% of subjects treated with sipuleucel-T were alive while only 11% of subjects treated with placebo were alive. D9902A provided supportive evidence that sipuleucel-T prolongs survival in this patient population (P=0.331, log rank; HR=1.3). A Cox PHR model analysis also resulted in a survival advantage for sipuleucel-T (P=0.023, Wald’s; HR=1.9). The integrated analysis of the data from D9901 and D9902A (n=225) showed a statistically significant survival benefit in the overall population based on the log rank analysis (P=0.011; HR=1.5) and a Cox PHR model (P=0.0006; HR=1.8). In both studies, sipuleucel-T was generally well tolerated with a consistent pattern of Grade 1 and 2 treatment-related adverse events lasting 1 to 2 days.
Conclusions: There are limited treatment options for patients with metastatic AIPC. Sipuleucel-T appears to provide a substantial survival advantage and a strong safety profile, suggesting a highly favorable benefit to risk ratio in this patient population.